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Donor cell leukemia arising from clonal hematopoiesis after bone marrow transplantation

Leukemia volume 30, pages 1916–1920 (2016)Cite this article

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Alterations in genes encoding epigenetic regulators are common in myeloid malignancies, and several recent studies have demonstrated that these mutations are present at high frequencies within peripheral blood cells in ~10% of individuals over 60 years of age. Although the presence of these mutations carries an increased risk of subsequent hematologic malignancies, the vast majority of individuals do not progress clinically and the natural history of clonal hematopoiesis is unclear.1, 2, 3 Thus, the term Clonal Hematopoiesis of Indeterminate Potential (CHIP) was proposed.4

Allogeneic bone marrow transplantation (alloBMT) remains the only curative therapy for many patients with hematologic malignancies. Over the past decade, advances in alloBMT have permitted older patients to successfully undergo the procedure. Accordingly, older matched sibling donors are being utilized. Moreover, the development of safe and effective haploidentical BMT allows parents to serve as related donors for their children.5 We hypothesized that clinically silent ‘premalignant’ clones (which do not result in overt malignancy under homeostatic conditions within the donor) may be subjected to substantial proliferative and self-renewal stress during the engraftment process and could undergo transformation. We report two cases of donor cell leukemia (DCL) arising from CHIP marked by somatic mutations in leukemia-related genes in donors over age 60 years.

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Acknowledgements

This work was supported by grants from the National Institute of Health (P01 CA015396) (RJJ) and (P30 CA006973), Edward P. Evans Foundation (LPG) and the Commonwealth Foundation. Next-generation sequencing was performed with the support of the Next Generation Sequencing Center in the Sidney Kimmel Comprehensive Cancer Center.

Author contributions

LPG, GZ, CDG, GG, WM and RJ designed the study. AED and ML helped with regulatory oversight and data collection. LPG and NT were responsible for clinical data collection. GZ, JE and CDG analyzed the bone marrow morphology, flow cytometric, cytogenetic and bone marrow engraftment data. VY performed next-generation DNA sequencing. RV, GZ and ML performed the statistical analysis. LPG, GZ, WM, CDG and RJ wrote the manuscript, which was edited and approved by all authors.

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Author notes

  1. L P Gondek, G Zheng, R Jones and C D Gocke: These authors contributed equally to this work.

Authors and Affiliations

  1. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    L P Gondek, G Ghiaur, A E DeZern, W Matsui, S Yegnasubramanian, M Levis, N Tucker & R Jones

  2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    G Zheng, M-T Lin, J R Eshleman & C D Gocke

  3. Division of Biostatistics, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    R Varadhan

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  1. L P Gondek
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Correspondence to L P Gondek.

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Gondek, L., Zheng, G., Ghiaur, G. et al. Donor cell leukemia arising from clonal hematopoiesis after bone marrow transplantation. Leukemia 30, 1916–1920 (2016). https://doi.org/10.1038/leu.2016.63

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